{"database":"GEO","file_versions":[{"headers":{"Content-Type":["application/json"]},"body":{"files":{"Other":["ftp://ftp.ncbi.nlm.nih.gov/geo/series/GSE293nnn/GSE293039/"]},"type":"primary"},"statusCode":"OK","statusCodeValue":200}],"scores":null,"additional":{"omics_type":["Transcriptomics"],"species":["Homo sapiens"],"gds_type":["Expression profiling by high throughput sequencing"],"full_dataset_link":["https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE293039"],"repository":["GEO"],"entry_type":["GSE"],"additional_accession":[]},"is_claimable":false,"name":"Dynamic JAK-STAT/IFN-signaling in subclinical to clinical T cell-mediated rejection following liver transplantation","description":"Subclinical rejection after liver transplantation precludes immunosuppression withdrawal despite normal clinical function. To better understand the immunobiology of early subclinical rejection, we performed longitudinal, multimodal immune profiling and single-cell RNA-sequencing (scRNA-seq) in adult living-donor recipients (n=13) participating in an interventional immunosuppression withdrawal trial. Samples from patients with subclinical rejection (termed “nonpermissive”) at 12 months post-transplant exhibited distinct immune trajectories from those with quiescent (“permissive”) allografts, despite comparable baseline profiles. Central to these distinct dynamics was biphasic Janus Kinase (JAK)/Signal Transducer and Activator of Transcription (STAT)-Interferon signaling. Greater interferon-stimulated gene (ISG) expression and JAK-STAT activation occurred post-reperfusion in permissive allograft recipients, which reversed at 12 months, when elevated ISG expression and JAK-STAT signaling was evident in nonpermissive recipients exhibiting subclinical rejection. We then leveraged our findings to ascertain whether a comparable signature existed in internal and external bulk RNA-seq and scRNA-seq liver transplant cohorts. Across cohorts, including a rodent model, there was a similar elevation in JAK-STAT signaling in instances of allograft rejection. We also detected distinct, portal-based phosphorylated STAT1 staining in a preliminary analysis of biopsies exhibiting histologic rejection compared with non-rejecting controls. Moreover, ruxolitinib-mediated JAK inhibition suppressed alloreactive CD8+ T cell proliferation and inflammatory-mediator production in vitro. Together, these exploratory findings suggest a temporal, biphasic role for JAK-STAT signaling in the regulation and occurrence of T cell-mediated rejection following liver transplant and highlight JAK inhibition as a potential therapeutic strategy.","dates":{"publication":"2026/08/26"},"accession":"GSE293039","cross_references":{"GSM":["GSM8874453","GSM8874454","GSM8874455","GSM8874456","GSM8874450","GSM8874451","GSM8874452","GSM8874457","GSM9581649","GSM9581648","GSM8874448","GSM8874449","GSM9581650","GSM9581651"],"GPL":["18573"],"GSE":["293039"],"taxon":["Homo sapiens"]}}